固相萃取-HPLC法研究格尔德霉素在Beagle犬药代动力学  

Pharmacokinetics of Geldanamycin in Beagle Dogs by Solid Phase Extraction-HPLC Method

作　　者：程春雷[1] 游雪甫[1] 王跃明[1] 张伟新[1] 娄人慧[1] 陈慧贞[1] 李电东[1] 蒋建东[1] 

机构地区：[1]中国医学科学院中国协和医科大学医药生物技术研究所,北京100050

出　　处：《药物分析杂志》2005年第4期409-412,共4页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金(39900184);国家十五重大科技专项资助项目(2003AA2Z347D)

摘　　要：目的:建立格尔德霉素在 Beagle 犬血浆中的同相萃取(SPE)-HPLC 测定方法,并研究其在犬体内的药代动力学。方法:18只 Beagle 犬分为0.25,0.5,1.0 mg·kg^(-1)低、中、高3个剂量组,单次静脉注射格尔德霉素,于给药后不同时间点采集血样。以 N-苯基-1-萘胺作为内标,Oasis HLB 同相萃取柱优化提取富集,HPLC 法测定其浓度;用药代动力学计算程序3P97拟合药物浓度-时间曲线,求算药动学参数。结果:格尔德霉素在0.01-1.0μg·mL^(-1)线性范围内,低、中、高3种不同浓度质控样品(0.01,0.1,1.0μg·mL^(-1))日内 RSD 分别为5.6%,4.6%,1.9%(n=5);日间 RSD 分别为6.9%,3.2%,6.7%(n=5)。绝对回收率分别为85.0%±3.0%,91.1%±2.2%,94.0%±0.7%(n=5);低、中、高剂量组的 T_(1/2β)分别为89.2,116.6,101.6 min;AUC 分别为6.9,12.7,24.9 min·μg·mL^(-1);Vc 分别为858.0,964.4,981.3 mL·kg^(-1);CL 分别为35.9,39.4,40.1mL·min^(-1)·kg^(-1)。结论:固相萃取-HPLC 法测定格尔德霉素准确,快速,回收率高。格尔德霉素在 Beagle 犬体内药代动力学符合二室静脉注射模型。这对以后的临床应用指导具有十分重要的意义。Objective:To develop a sensitive and specific solid phase extraction (SPE)-HPLC method for detec- ting geldanamycin in Beagle dog plasma and to study its pharmacokinetics in Beagle dogs by iv injection.Methods: 18 Beagle dogs were divided into 3 groups,randomly,and the dose of geldanamycin were 0.25,0.5,1.0 mg·kg^(-1) with single iv injection.Plasma samples with addition of N-pheny-1-naphennamine as internal standard were extracted and purified using Oasis HLB cartridge by optimized SPE,and the concentrations of geldanamycin were detected by HPLC.The parameters of pharmacokinetic were calculated by Practical Pharmacokinetic Program 3P87. Results:The calibration curve was linear with range from 0.01 μg·mL^(-1) to 1.0μg·mL^(-1).The concentrations of the cheek samples were 0.01,0.1 and 1.0 μg·mL^(-1).The intra-day(n=5) and inter-day(n=5)precisions (RSD) of check samples were 5.6%,4.6%,1.9% and 6.9%,3.2%,6.7%,respectively.The recoveries of check samples (n=5) were 85.0%±3.0%,91.1%±2.2 %,94.0%±0.7 %,respectively.The pharmacokinetic param- eters of geldanamycin in Beagle dogs at doses of 0.25,0.5 and 1mg·kg^(-1) were as follows:T_(1/2β) were 89.2,116.6 and 101.6 min;AUC were 6.9,12.7,24.9 min·μg·mL^(-1);Vc were 858,964 and 981 mL^(-1)·kg;CL were 35.9, 39.4 and 40.1 mL·min^(-1)·kg`(-1).Conclusion:The SPE-HPLC method for geldanamycin is accurate,rapid and simple with good reproducibility.The pharmacokinetics of geldanamycin in Beagle dogs fit two-compartment mod- el.This method and result provided basis for clinical application.

关 键 词：固相萃取-HPLC法 BEAGLE犬 格尔德霉素 HPLC测定方法 浓度-时间曲线 体内药代动力学 单次静脉注射 药动学参数 不同时间 优化提取 计算程序 线性范围 质控样品 不同浓度 临床应用 RSD 回收率 犬血浆 犬体内 高剂量 AUC 

分 类 号：R971.3[医药卫生—药品] R969.1[医药卫生—药学]